Fragility of overactive bladder medication clinical trials: A systematic review.

Autor: Li KD; Department of Urology, University of California San Francisco, San Francisco, California, USA.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA., Venishetty N; Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA., Fernandez AM; Department of Urology, University of California San Francisco, San Francisco, California, USA., Hakam N; Department of Urology, University of California San Francisco, San Francisco, California, USA., Ghaffar U; Department of Urology, University of California San Francisco, San Francisco, California, USA., Gupta S; Department of Urology, University of California San Francisco, San Francisco, California, USA., Patel HV; Department of Urology, University of California San Francisco, San Francisco, California, USA., Breyer BN; Department of Urology, University of California San Francisco, San Francisco, California, USA.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
Jazyk: angličtina
Zdroj: Neurourology and urodynamics [Neurourol Urodyn] 2024 Sep; Vol. 43 (7), pp. 1523-1533. Date of Electronic Publication: 2024 Apr 09.
DOI: 10.1002/nau.25468
Abstrakt: Purpose: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied.
Materials and Methods: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression.
Results: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001).
Conclusions: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.
(© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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